Expression of DGCR8-dependent microRNAs is indispensable for osteoclastic development and bone-resorbing activity

Toshifumi Sugatani, Blake E. Hildreth, Ramiro E. Toribio, Hartmut H. Malluche, Keith A. Hruska

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Recently, microRNAs (miRs) have been implicated in bone formation and homeostasis. We previously reported that Dicer generated miRs have pivotal roles in differentiation and activity of osteoclasts. However, recent studies have demonstrated that Dicer is implicated in production of endogenous small interfering RNAs, non-canonical miRs, and other small RNAs in mammals. Hence, a challenging question is the extent to which expression of canonical miRs is obligatory for osteoclastic control of bone metabolism. DiGeorge syndrome critical region gene 8 (DGCR8) is exclusively related to expression of miRs by a canonical processing pathway together with the nuclear RNase III enzyme Drosha. Osteoclast-specific deletion of DGCR8 led to impaired osteoclastic development and bone resorption so that bone development was significantly retarded. In culture, the expression levels of osteoclastic phenotype-related genes and proteins were remarkably inhibited during osteoclastogenesis in DGCR8-deficiency. Thus, we have identified that DGCR8-dependent miRs are indispensable for osteoclastic control of bone metabolism.

Original languageEnglish
Pages (from-to)1043-1047
Number of pages5
JournalJournal of cellular biochemistry
Volume115
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • DGCR8
  • Dicer
  • microRNA
  • osteoclast

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